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A multicentre, open-label phase II study of Irinotecan, capecitabine (Xeloda®), and Oxaliplatin (IXO) as first-line treatment in patients with metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma

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Summary

Purpose Chemotherapy remains the primary treatment for metastatic gastric/GEJ cancer but optimal agents and schedule remain controversial. This study examined the safety and efficacy of first-line Irinotecan, capecitabine (Xeloda®), and Oxaliplatin (IXO). Patients and Methods Eligible patients with HER2-unamplified/unknown, metastatic gastric/GEJ adenocarcinoma were treated with 21-day cycle IXO at dose level 1 (DL1: Day 1 O-100 mg/m2 & I-160 mg/m2 IV, Day 2–15 X-1900 mg/m2/day PO divided doses) or modified IXO (mIXO): Day 1 O-85 mg/m2 & I-120 mg/m2 IV, Day 2–15 X-1425 mg/m2/day PO divided doses). This Bryant and Day two-stage designed study had dual primary endpoints of objective response rate (ORR) and toxicity. Secondary endpoints were overall survival (OS) and progression-free survival (PFS). Results Fifty patients were enrolled and received a median of 7 cycles. After accrual of 9 patients at DL1, evaluable RR was 88% however dose limiting toxicity (DLT) rate was 56% thus doses were adjusted to mIXO. Fifteen patients accrued at mIXO had a RR of 60% and DLT rate of 13% allowing continuation to stage 2. Overall, 48 and 49 patients were evaluable for efficacy and safety, respectively, with ORR of 54% and DLTs in 24% of patients (DL1 = 56%; mIXO = 18%). Disease control rate was 85%. The most frequent grade 3/4 adverse events were diarrhea, neutropenia, fatigue, hypokalemia, and nausea. Median PFS and OS were 7.5 and 13.0 months, respectively, with a median follow-up of 9.7 months. Conclusion mIXO demonstrates promising ORR, PFS, OS, and acceptable toxicity compared to standard triplet regimens. IXO should be evaluated in phase III trials.

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Acknowledgements

We would like to thank the patients and their families. We also thank the research staff at participating sites, especially SeeSee Raynard and Kristine Young.

Funding

Funding for this investigator sponsored study was provided by Roche and Sanofi.

Author information

Author notes

  1. Hagen Kennecke

    Present address: Medical Oncology, Virginia Mason Cancer Institute, Seattle, WA, USA

  2. Anthony Fields

    Present address: Department of Oncology, University of Alberta, Edmonton, AB, Canada

Authors and Affiliations

  1. Medical Oncology, Cross Cancer Institute, 11560 University Avenue, Edmonton, AB, T6G 1Z2, Canada

    Arthur Lui, Karen Mulder, Larissa Vos, Sunita Ghosh, Anthony Fields & Jennifer Spratlin

  2. Medical Oncology, St. Michael’s Hospital, Toronto, ON, Canada

    Christine Brezden-Masley

  3. Medical Oncology, Ottawa Hospital, Ottawa, ON, Canada

    Michael Vickers, Rakesh Goel, Horia Marginean & Jean Maroun

  4. Medical Oncology, Tom Baker Cancer Centre, Calgary, AB, Canada

    Jose Monzon

  5. Medical Oncology, British Columbia Cancer Agency, Vancouver, BC, Canada

    Hagen Kennecke

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  1. Arthur Lui
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Corresponding author

Correspondence to Jennifer Spratlin.

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Conflict of interest

Karen Mulder has consulting or advisory role from Novartis, Lilly and LEO Pharma, research funding from Amgen, Roche, Bayer, & Sanofi Canada; Christine Brezden-Masley has honoraria from Roche, consulting or advisory role from Roche, research funding from Roche; Michael Vickers has honoraria from Ipsen, Lilly, Novartis, & Celgene, consulting or advisory role from AstraZeneca; Jose Monzon has consulting or advisory role from Bristol-Myers Squibb, Celgene, Merck, Novartis, & Roche, speakers’ bureau from Bristol-Myers Squibb & Merck; Jennifer Spratlin has honoraria from Lilly, Celgene Taiho & Astellas, consulting or advisory role from Lilly, Celgene, Taiho & Astellas, and research funding from Sanofi, Roche, & Celgene. All other authors have nothing to disclose.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Lui, A., Mulder, K., Brezden-Masley, C. et al. A multicentre, open-label phase II study of Irinotecan, capecitabine (Xeloda®), and Oxaliplatin (IXO) as first-line treatment in patients with metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. Invest New Drugs 36, 674–682 (2018). https://doi.org/10.1007/s10637-018-0599-4

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